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Open-Label Extension Study of Kuvan for Autism

This study has been completed.
Sponsor:
Collaborator:
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Glen R. Elliott, The Children's Health Council
ClinicalTrials.gov Identifier:
NCT00943579
First received: July 20, 2009
Last updated: July 2, 2013
Last verified: July 2013
  Purpose

This is an open-label extension study available only to subjects who completed an earlier double-blind, placebo-controlled study of sapropterin in children with autism. During this protocol, all subjects will be receiving brand-name Kuvan 20 mg/kg/day for 16 weeks; subject who complete the first 16 weeks will have the option of continuing on Kuvan at the same dose for up to 90 days after the last subject has completed the first 16 weeks of this protocol. The purpose of the study primarily is to gather additional information on safety and efficacy in this population.


Condition Intervention Phase
Autistic Disorder
Drug: Kuvan®
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Kuvan® (Sapropterin) as a Treatment for Autistic Disorder: An Open Label Extension Protocol

Resource links provided by NLM:


Further study details as provided by The Children's Health Council:

Primary Outcome Measures:
  • Clinical Global Impressions Scale [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    This is a summary judgment made by a trained clinician based on observed and reported behaviors of the child compared to baseline. It is a 7-point scale (1) very much improved, (2) much improved, (3) minimally improved (4) no change, (5) minimally worse, (6) much worse and (7) very much worse. Chi-square analyses were used to assess change in CHI-I scores (by group, post-test)Mixed-effects regression models determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. The mixed-effects regression model is robust to data dependency that occurs with the repeated assessments of individuals over time & can handle missing data. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time


Secondary Outcome Measures:
  • Vineland Adaptive Behavior Scale, 2nd Edition [ Time Frame: Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). ] [ Designated as safety issue: No ]
    The Vineland-2 is semi-structured interview designed to communication, daily living, socialization and motor skills. The Vineland-2 is comprised of a total Adaptive Composite Scale; we chose to use 10 subscales that specifically address functional domains relevant for a young ASD sample - Receptive Communication, Expressive Communication, Personal Daily Living Skills, Domestic Daily Living Skills, Community Daily Living Skills, Interpersonal Relations, Play Skills, Coping Skills, Gross Motor Skills, Fine Motor Skills. The scales generate raw or sum, V-, and age-equivalent scores; raw scores were selected for use in this study. Higher subscale scores indicate more skills. Raw scores can range from 0 to 766 for the overall adaptive behavior composite. Subscales are combined to form the overall Adaptive Behavior Composite, which is essentially a weighted average of the various subscales combined.

  • Children's Yale Brown Obsessive Compulsive Scale [ Time Frame: Weeks 8 & 16 ] [ Designated as safety issue: No ]
  • Parental Global Assessment [ Time Frame: Weeks 8 & 16 ] [ Designated as safety issue: No ]
  • Preschool Language Scale, 4th Edition (PLS-4) [ Time Frame: Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). ] [ Designated as safety issue: No ]
    Measures expressive & receptive language and total scores in ages 0 to 6 years 11 months. The scales generate raw, standard, and age-equivalent scores; raw scores for the total scale were selected for use in this study. Total is average of subscales. Minimum raw score = 0, maximum = 130. Higher raw scores indicate better language skills. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept & trend modeling that accounts for each individual's initial level of symptom severity/functioning & rate of change/time

  • Connor's Preschool ADHD Questionnaire [ Time Frame: Weeks 8 & 16 ] [ Designated as safety issue: No ]
  • Aberrant Behavior Checklist (ABC) [ Time Frame: Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). ] [ Designated as safety issue: No ]
    This is a 58-item informant-based, factor-analyzed scale comprised of a total scale and 5 subscales that generate raw scores. Scores based on a likert scale ranging from 0-3 where 0 is not a problem to 3 where the problem is severe. Subscales include: Irritability, Social Withdrawal, Stereotypic Behaviors, Hyperactivity and Inappropriate Speech. Total maximum score is 174. Higher subscale scores indicate more symptoms. Scores are totaled to compute subscale scores. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time

  • Adverse Events Reporting [ Time Frame: Cummulative throughout study ] [ Designated as safety issue: Yes ]

Enrollment: 41
Study Start Date: August 2009
Study Completion Date: March 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Kuvan®
Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks.
Drug: Kuvan®
Brand-name Kuvan® (sapropterin) will be administered to all subjects at a dose of 20 mg/kg/day for 16 weeks.
Other Names:
  • Kuvan®
  • sapropterin
  • tetrahydrobiopterin

Detailed Description:

This is an open-label extension study available only to subjects who completed an earlier double-blind, placebo-controlled study of sapropterin in children with autism. During this protocol, all subjects will be receiving brand-name Kuvan 20 mg/kg/day for 16 weeks; subject who complete the first 16 weeks will have the option of continuing on Kuvan at the same dose for up to 90 days after the last subject has completed the first 16 weeks of this protocol. The purpose of the study primarily is to gather additional information on safety and efficacy in this population.

  Eligibility

Ages Eligible for Study:   3 Years to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All subjects must have completed earlier trial, CHC 0901 (NCT00850070)
  • Parents must be willing and able to sign informed consent

Exclusion Criteria:

  • Child failed to complete CHC 0901 (NCT00850070)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943579

Locations
United States, California
The Children's Health Council
Palo Alto, California, United States, 94304
Sponsors and Collaborators
The Children's Health Council
BioMarin Pharmaceutical
Investigators
Principal Investigator: Glen R Elliott, PhD, MD The Children's Health Council
  More Information

No publications provided

Responsible Party: Glen R. Elliott, Chief Psychiatrist and Medical Director, The Children's Health Council
ClinicalTrials.gov Identifier: NCT00943579     History of Changes
Other Study ID Numbers: CHC-0902
Study First Received: July 20, 2009
Results First Received: January 16, 2013
Last Updated: July 2, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by The Children's Health Council:
autism
autistic disorder
tetrahydrobiopterin
sapropterin
treatment

Additional relevant MeSH terms:
Autistic Disorder
Disease
Child Development Disorders, Pervasive
Mental Disorders
Mental Disorders Diagnosed in Childhood
Pathologic Processes

ClinicalTrials.gov processed this record on November 25, 2014